Due to the mutation-specific nature of the exon skipping approach, only subsets of patients are eligible for the skipping of a certain exon, leading to clinical trials generally being conducted in small cohorts of patients. This harbours the risk of significant treatment-induced changes being masked by inter patient variability. The lack of objective functional outcome measures increases this risk even further. At the moment the most commonly used functional measure used as a primary endpoint in clinical trials for DMD is the 6 minute walk test (6MWD), where the outcome may be influenced by patient’s motivation especially in non-placebo controlled trials. The identification of functional and molecular outcome measures makes it able to monitor disease progression and treatment response is a priority for the field, also to avoid invasive muscle biopsies that are often required upon trial participation and which constitute a burden for patients and their families.
The focus of our Biomarker group is to:
- Explain the inter-individual variability by identifying and validating genetic modifiers
- Identify and validate non-invasive biomarkers to be used as surrogate endpoints in clinical trials
We use a multidisciplinary approach to identify and validate molecular biomarkers in patients’ samples and back up the obtained results with data obtained in animal models. We make us of genomic platforms (next generation sequencing and mass spectrometry) to identify DNA changes which modify disease progression. Transcriptomic, proteomic and metabolomic platforms (next generation sequencing, mass spectrometry, immunoassays) are used to identify molecular signatures in body fluids to describe disease progression. The identified markers are validated with independent techniques in independent samples. This approach is used to identify common disease signatures in several neuromuscular condition and to identify therapeutic candidates. In fact, our work does not only involve Duchenne but also other neuromuscular disorders such as Becker muscular dystrophy, limb girdle muscular dystrophies, congenital muscular dystrophies, facioscapulohumeral muscular dystrophy, myasthenia gravis and sporadic inclusion body myositis where the cause of the disease is different, but pathophysiological changes are somewhat similar.